The proposed study involves synthesis of antisense S-oligonucleotides specific to alpha, beta and gamma protein kinase C mRNA's. These oligonucleotides will be used as a tool for selective inhibition of gene expression by inhibiting PKC translation. Experiments will be conducted to establish that the synthetic oligonucleotides inhibit translation of a specific PKC-mRNA without affecting translation of the other PKC-mRNA's or overall translation. Detailed experiments will be conducted in HL60 cells to determine the turnover of alpha/ beta PKC-mRNA's during differentiation in response to PMA, DMSO, Vitamin D3 and retinoic acid. Optimal conditions for introducing specific PKC oligonucleotides into HL60 cells in culture will be conducted and their effect on translation determined. Lastly, we will examine whether inhibiting translation of either of the three PKC- mRNA's has an effect on the ability of HL60 cells to enter a differentiation program in response to a specific inducer. This study will provide information regarding differential regulation of PKC isoform expression and a means to examine the functional heterogeneity of this gene family.